The ability to control protein localization and activity would be enormously beneficial for understanding and modulating protein function in physiological processes. Several approaches have been developed previously for optical control of protein activity using natural proteins and protein domains that change conformation upon light absorption, for example, using proteins such as rhodopsins, phytochromes, and cryptochromes, and LOV domains from phototropins and FKF1 (Airan et al. (2009) Nature 458:1025-1029; Inoue et al. (2005) Nat. Methods 2:415-418; Kennedy et al. (2010) Nat. Methods 7:973-975; Levskaya et al. (2009) Nature 461:997-1001; Szobota et al. (2007) Neuron 54:535-545; Wu et al. (2009) Nature 461:104-108; and Yazawa et al. (2009) Nat. Biotechnol. 27:941-945). However, widespread implementation of these methods has been hindered by various problems, including the limited applicability of the methods to only specific signaling pathways (Airan et al., supra), the need for exogenous cofactors (Levskaya et al., supra), slow kinetics of induction (Yazawa et al., supra), undesirable light-independent dimerization (Kennedy et al., supra), or the toxicity of light at blue wavelengths (Szobota et al., supra; Wu et al., supra; Yazawa et al., supra). Furthermore, of all these strategies, only fusion to LOV domains has been used to control the activity of a single protein, but this method generally requires extensive customization (Wu et al., supra; Strickland et al. (2008) Proc. Natl. Acad. Sci. U.S.A. 105:10709-10714; Strickland et al. (2010) Nat. Methods 7:623-626; and Wu et al. (2011) Methods Enzymol. 497:393-407). In addition, none of these light-absorbing domains are capable of controlling both protein localization by intermolecular interactions and function of a single polypeptide chain.
Thus, there remains a need for a simple to use system for controlling protein localization and activity with light, which can be readily applied to a wide range of proteins.